文章基本信息

标题：ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic
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作者：Maya Braun ; Elad Sharon ; Irene Unterman 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：8
页码：1-19
DOI：10.1016/j.isci.2020.101384
语种：English
出版社：Elsevier
摘要：SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We identified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.Graphical AbstractDisplay OmittedHighlights•Mapping the ACE2 conservation pattern in 146 mammal reservoirs and 1,671 eukaryotes•Identification of genes that show a similar evolutionary pattern as ACE2•Generation of an ACE2 protein network using co-evolution and data integration•Drugs-to-network analyses mapped 145 drugs that perturbed the ACE2 networkClassification of Proteins; Evolutionary Mechanisms; Virology